The Slx4 protein is a heteromeric structure-specific endonuclease found from fungi to mammals. Slx4 is a regulatory subunit of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination [, ]. The SLX1-SLX4 complex has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs) [, ]. Defects in SLX4 are the cause of Fanconi anemia complementation group P (FANCP), which is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia [, ].
The Slx4 protein is an endonuclease involved in processing DNA. In Saccharomyces cerevisiae, Slx4 forms complex with Slx1 that acts as a nuclease on branched DNA substrates, particularly simple-Y, 5'-flap, or replication fork structures by cleaving the strand bearing the 5' non-homologous arm at the branch junction and thus generating ligatable nicked products from 5'-flap or replication fork substrates [, ]. It is also involved in interstrand cross-link repair and in Rad1/Rad10-dependent processing of recombination intermediates[].
The Fanconi Anemia (FA) pathway is responsible for interstrand crosslink DNA repair []. The name originates the recessive syndrome known as Fanconi anemia, which causes developmental problems and cancer predisposition []. In this pathway, the FANCI-FANCD2 (ID) complex is ubiquitinated by the FA core complex and then travels to sites of damage to coordinate repair [, ]. FA pathway activation seems to trigger dissociation of FANCD2 from FANCI, coinciding with FANCD2 monoubiquitination which precedes monoubiquitination of FANCI []. This suggests a functional separation for FANCD2 from FANCI [].Monoubiquitinated FANCD2 functions to recruit DNA repair factors FAN1 (Fanconi-associated nuclease 1) []and SLX4 [], suggesting that chromatin-bound FANCD2Ub is a docking platform for certain DNA repair nucleases. FANCD2 has also a role in replication fork recovery [].
